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An audit of the use of etidronate and oestrogen therapy in the management of established osteoporosis
45
EFFECTS OF PAMIDRONATE IN OSTEOPENIA. B.L.Lanudahl.
HIGH-TURNOVER
L.S.Mortensen, E.F.Eriksen. P-CharlesAarhusBoneandMineralResearch &OIJP. University Amtssygehus, DK-19000
Deparlmeni Aarhus
01 Endocrinology, C. Denmark.
Aarhus
Pamidronate is a potent inhibitor of bc,ne resorption.Three patients with high-turnover osteopeniawas treatedwith pamidronate. The three patients (1 f$emale(33years), 2 males(24,49 years)) had low BMD (QDR): beliaw 3.4 SD for age, high excretion in urine :,f hydroxyproline and calcium. (Ine patient had elevatedalkalinephosphatasein serum. ~11 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, headache and fatigue during the first week of treatment. One patient had intermittent bone g~2n CInti ng the treatment. Results: A decrease in calcium excretion: 0.23 vs. 0.36 mmol/umolcreatinine/day (38 %),max. effect after I31 days. A decrease in hydroxyproline excretion: 11.74 vs. 20.35 umol/umol 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 femoralneck. These preliminaryresults suggest, that high3e treated turnover osteopenia could succesfullywith pamidronate in .acombination of i.v.infusion (0.5 mg/kg) followed by oral administration for 3 months (300 mg/day) 41 INCREASEIN BONE MINERALDENSITY AID DURATION OF ANTIRESORPTIVE TREATM!lNTIN ESTABLISHED WSTMENOPAUSAL OSTEOPOROSIS. M.Hontaqnani, D.Agnusdei, C.CePollaro, F.Zacchei, R.Civitelli, C.Gennari. Institute of Internal Medicine, University of Siena, Italy. In active osteoporosis the rate of bone resorption (ER) exceeds that of bone formation (BF). The observation that treatment of osteo,Porosis with inhibitors of BR may result in non-linear rates of change of bone mass indicates that there are differences between the rates of change of BF snd BR. These drugs may produce during the first period of treatment a rise in bone mass due to a suppression of 8~ and continued BF, but, since the inhibitors of BR eventually inhibit also BF, the increase 3f bone mass may be transient. To test this hypothesis, we followed the changes of the bone m. neral content of the lumbar spine (BMC) produced by a l?lg-term treatment such as ~01% jugated estrogens with anti-resorptive drugs, salmon calcitonin (sCT) and die hloromethylene(R). bisphosphonate (Cl%MDP) in patients hith established We treated for 4 years 11 postmenopausal c steoporosis. patients with sCT (50 IU i.m. every ;?nd day for 3 months 10 patients with E (0.625 mg/d on and 3 monrhs off), ar,d 8 patients with C12MOP (800 mg/d for 3 continuously), months on and 3 months off). Results are reportedbelow. Treatment B;4a:% increase-vs. basal valuesi Final Value (48 mo.1 Time SC’P +2.71 +1.86 180.
+1.e1 18 mo. C12MDP 44.38 +2.41 24 mo. E +2.55 In all cases we obtained a gain in skeletal mass of about 3 to 5% of time of 2 years. After this 0 over a period
period a new steady-state was achieved and during the 4th year of treatment a plateau was reached with E, while the bone mass decreased with sCT and C12MDP. These observations suggest that the increase in bone mass with anti-resorpt ive drugs cannot be obtained and that long-term studies are required when perpetuated, usina bone mass as a criterion to test the efficacy of these drugs in established osteoporosis.
46 BONE HISTOMORPHlXlETRY AFTER LUNS-TERM TREATMENT WITH CYcLICElL PHBSPHCIRUS CIND ETIDRONATE. P. Miller. W. Huffer. D. McIntyre. M. YanoveryM. Anaer. M. Harrison. D. Gillum. University of Colorado Health Sciences Center, Denver, Colorado. USCI. To assess the safety and efficacy of chronic cyc!ical phosphorus and eridronate (p/etid) usage, nine patients with postmenopausal osteopcr-osis (PM01 had bone histomorphometry and axial bone densitometry (DPe) both before and six years after twenty treatment cycles. Six agematched patients with PMO, who received only calcium, served as controls. Results: p/etid Control (n--91 (n=6) Base1 ine h Years Baseline 4 Year5 ji?SE kSE Z^SE K&SE (?S/SS(::! X.9.$4.7 32.6c6.9) 3C . 5.>-4.3 I 35.7;3.07 11.922.0 O.Th(u) 10.921.2 ll.lt1.9 li.9ff.9 fljAR(u/d)0.31+.04 0.3lk.03 0.26+.04 0.27Z.05 RLT(days)32.7+7.5 43.425.9 46.4.?0.3 49.129.7 MS/BS(%) 12.422.9 15.5k3.8 13.2+1.8 14.2Z2.5 MS/OSt%) 49.4Z10.5 50.6fS.2 28.2f2.2 32.Of3.1 (rCp~.O3% within p/etid group1 The bone mineral density increased 11.9 9 4% in th@ p/etid group (pC.OZI and increased 7.7 + 3% in the control group (NS). The height did not change within the pletid group while the height significantly decreased in the control pro Ap (R-1.3” f .04”, p<.O4). We conclude that longterm therapy with p/etid is safe, does not cause increases bone mass, and preserves ostecmalacia. ,height in PMO.
48 AN AUDIT OF
THE USE OF ETIDRONATEAND OESTROGEN THERAP’!
OF ESTABLISHEL)OSTEOPOROSIS IN THE MANAGEMENT MTA Rehman. RW Whitehouse*, DC Anderson
JE Adams*,
P Selby,
Bone Disease Research Centre. University of Manchester and Drpariments of Medicine, Salford, and Disgncstic Radiology , The Medical School, Manchester, IJR The management of established osteoporosis is unsatisfactory. This preliminary study vas undertaken to assess the effect of three treatment regimes (Croup l-cyclical etidronate 400 mg daily for 4 days each month; Group Z-hormone replacement therapy [HRT]; Group 3combination of both therapies) in patients uith established osteoporosis (BMD < -2bD below peak mass or vertebral fracture). Eighty two patients have entered ehe study - 0 men and 74 women (mean age 48 and 62 years respectively). Side effects necessitated withdrawal of etidronate in 3 (7.5%) patients and of HRT in 5 (10%). E,une mineral density measurements (B!O) were m;ldc using QCT, SPA and DXA and to date 1 year follow up measurements are available in 28 patients (group L = 9; group 2 - 15; group 3 = 4). QCT fncrex=d in all groups but was significant only in group 1 (change of + 2.9 mg/ml from mean baseline BMD of 34.4 lug/ml; p < 0.01). SPA incr,eased significantly only iy group 2 (chauge of + 0.02 g/cm2 from mean 0.32 g/cm ; p < 0.04). DXA of lumbar spine anrr femoral neck showed no significant change. CONCLUSION:This method of cyclical adminstracion of etidronate was well tolerated. These preliminary results suggest a small but significant increase fn BMDwith enhanced by the combination with HRT requires further study.
S23
EFFECTS OF PAMIDRONATE IN OSTEOPENIA. B.L.Lanudahl.
HIGH-TURNOVER
L.S.Mortensen, E.F.Eriksen. P-CharlesAarhusBoneandMineralResearch &OIJP. University Amtssygehus, DK-19000
Deparlmeni Aarhus
01 Endocrinology, C. Denmark.
Aarhus
Pamidronate is a potent inhibitor of bc,ne resorption.Three patients with high-turnover osteopeniawas treatedwith pamidronate. The three patients (1 f$emale(33years), 2 males(24,49 years)) had low BMD (QDR): beliaw 3.4 SD for age, high excretion in urine :,f hydroxyproline and calcium. (Ine patient had elevatedalkalinephosphatasein serum. ~11 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, headache and fatigue during the first week of treatment. One patient had intermittent bone g~2n CInti ng the treatment. Results: A decrease in calcium excretion: 0.23 vs. 0.36 mmol/umolcreatinine/day (38 %),max. effect after I31 days. A decrease in hydroxyproline excretion: 11.74 vs. 20.35 umol/umol 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 femoralneck. These preliminaryresults suggest, that high3e treated turnover osteopenia could succesfullywith pamidronate in .acombination of i.v.infusion (0.5 mg/kg) followed by oral administration for 3 months (300 mg/day) 41 INCREASEIN BONE MINERALDENSITY AID DURATION OF ANTIRESORPTIVE TREATM!lNTIN ESTABLISHED WSTMENOPAUSAL OSTEOPOROSIS. M.Hontaqnani, D.Agnusdei, C.CePollaro, F.Zacchei, R.Civitelli, C.Gennari. Institute of Internal Medicine, University of Siena, Italy. In active osteoporosis the rate of bone resorption (ER) exceeds that of bone formation (BF). The observation that treatment of osteo,Porosis with inhibitors of BR may result in non-linear rates of change of bone mass indicates that there are differences between the rates of change of BF snd BR. These drugs may produce during the first period of treatment a rise in bone mass due to a suppression of 8~ and continued BF, but, since the inhibitors of BR eventually inhibit also BF, the increase 3f bone mass may be transient. To test this hypothesis, we followed the changes of the bone m. neral content of the lumbar spine (BMC) produced by a l?lg-term treatment such as ~01% jugated estrogens with anti-resorptive drugs, salmon calcitonin (sCT) and die hloromethylene(R). bisphosphonate (Cl%MDP) in patients hith established We treated for 4 years 11 postmenopausal c steoporosis. patients with sCT (50 IU i.m. every ;?nd day for 3 months 10 patients with E (0.625 mg/d on and 3 monrhs off), ar,d 8 patients with C12MOP (800 mg/d for 3 continuously), months on and 3 months off). Results are reportedbelow. Treatment B;4a:% increase-vs. basal valuesi Final Value (48 mo.1 Time SC’P +2.71 +1.86 180.
+1.e1 18 mo. C12MDP 44.38 +2.41 24 mo. E +2.55 In all cases we obtained a gain in skeletal mass of about 3 to 5% of time of 2 years. After this 0 over a period
period a new steady-state was achieved and during the 4th year of treatment a plateau was reached with E, while the bone mass decreased with sCT and C12MDP. These observations suggest that the increase in bone mass with anti-resorpt ive drugs cannot be obtained and that long-term studies are required when perpetuated, usina bone mass as a criterion to test the efficacy of these drugs in established osteoporosis.
46 BONE HISTOMORPHlXlETRY AFTER LUNS-TERM TREATMENT WITH CYcLICElL PHBSPHCIRUS CIND ETIDRONATE. P. Miller. W. Huffer. D. McIntyre. M. YanoveryM. Anaer. M. Harrison. D. Gillum. University of Colorado Health Sciences Center, Denver, Colorado. USCI. To assess the safety and efficacy of chronic cyc!ical phosphorus and eridronate (p/etid) usage, nine patients with postmenopausal osteopcr-osis (PM01 had bone histomorphometry and axial bone densitometry (DPe) both before and six years after twenty treatment cycles. Six agematched patients with PMO, who received only calcium, served as controls. Results: p/etid Control (n--91 (n=6) Base1 ine h Years Baseline 4 Year5 ji?SE kSE Z^SE K&SE (?S/SS(::! X.9.$4.7 32.6c6.9) 3C . 5.>-4.3 I 35.7;3.07 11.922.0 O.Th(u) 10.921.2 ll.lt1.9 li.9ff.9 fljAR(u/d)0.31+.04 0.3lk.03 0.26+.04 0.27Z.05 RLT(days)32.7+7.5 43.425.9 46.4.?0.3 49.129.7 MS/BS(%) 12.422.9 15.5k3.8 13.2+1.8 14.2Z2.5 MS/OSt%) 49.4Z10.5 50.6fS.2 28.2f2.2 32.Of3.1 (rCp~.O3% within p/etid group1 The bone mineral density increased 11.9 9 4% in th@ p/etid group (pC.OZI and increased 7.7 + 3% in the control group (NS). The height did not change within the pletid group while the height significantly decreased in the control pro Ap (R-1.3” f .04”, p<.O4). We conclude that longterm therapy with p/etid is safe, does not cause increases bone mass, and preserves ostecmalacia. ,height in PMO.
48 AN AUDIT OF
THE USE OF ETIDRONATEAND OESTROGEN THERAP’!
OF ESTABLISHEL)OSTEOPOROSIS IN THE MANAGEMENT MTA Rehman. RW Whitehouse*, DC Anderson
JE Adams*,
P Selby,
Bone Disease Research Centre. University of Manchester and Drpariments of Medicine, Salford, and Disgncstic Radiology , The Medical School, Manchester, IJR The management of established osteoporosis is unsatisfactory. This preliminary study vas undertaken to assess the effect of three treatment regimes (Croup l-cyclical etidronate 400 mg daily for 4 days each month; Group Z-hormone replacement therapy [HRT]; Group 3combination of both therapies) in patients uith established osteoporosis (BMD < -2bD below peak mass or vertebral fracture). Eighty two patients have entered ehe study - 0 men and 74 women (mean age 48 and 62 years respectively). Side effects necessitated withdrawal of etidronate in 3 (7.5%) patients and of HRT in 5 (10%). E,une mineral density measurements (B!O) were m;ldc using QCT, SPA and DXA and to date 1 year follow up measurements are available in 28 patients (group L = 9; group 2 - 15; group 3 = 4). QCT fncrex=d in all groups but was significant only in group 1 (change of + 2.9 mg/ml from mean baseline BMD of 34.4 lug/ml; p < 0.01). SPA incr,eased significantly only iy group 2 (chauge of + 0.02 g/cm2 from mean 0.32 g/cm ; p < 0.04). DXA of lumbar spine anrr femoral neck showed no significant change. CONCLUSION:This method of cyclical adminstracion of etidronate was well tolerated. These preliminary results suggest a small but significant increase fn BMDwith enhanced by the combination with HRT requires further study.
S23