Biochemical and radiologic improvement in Paget's disease of bone treated with alendronate: A randomized, placebo-controlled trial

被引:131
作者
Reid, IR
Nicholson, GC
Weinstein, RS
Hosking, DJ
Cundy, T
Kotowicz, MA
Murphy, WA
Yeap, S
Dufresne, S
Lombardi, A
Musliner, TA
Thompson, DE
Yates, AJ
机构
[1] UNIV MELBOURNE, GEELONG HOSP, GEELONG, VIC, AUSTRALIA
[2] UNIV ARKANSAS MED SCI HOSP, LITTLE ROCK, AR USA
[3] CITY HOSP NOTTINGHAM, NOTTINGHAM, ENGLAND
[4] UNIV TEXAS, MD ANDERSON CANC CTR, HOUSTON, TX USA
[5] MERCK RES LABS, RAHWAY, NJ USA
关键词
D O I
10.1016/S0002-9343(96)00227-6
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
PURPOSE: The potent bisphosphonates offer great promise in the management of Paget's disease of bone, but are currently available only as parenteral preparations in most countries. There is a need for a well-tolerated, oral therapy. Furthermore, none of the currently available therapies have been rigorously demonstrated to heal the lytic bone lesions characteristic of this condition. Alendronate is a potent new oral aminobisphosphonate that has shown promising effects on Paget's disease in preliminary studies. METHODS: We report a double-blind, randomized comparison of oral alendronate 40 mg/day and placebo over 6 months in 55 patients with Paget's disease. Efficacy was determined from measurements of biochemical indices of bone turnover (serum alkaline phosphatase and urine N-telopeptide) and blinded radiologic assessment of lytic bone lesions. RESULTS: N-telopeptide excretion declined by 86% and serum alkaline phosphatase by 73% in patients receiving alendronate, but remained stable in patients receiving placebo (P <0.001 between groups for both indices). Responses were similar whether or not patients had previously received bisphosphonate treatment. Alendronate treatment normalized alkaline phosphatase in 48% of patients. Forty-eight percent of alendronate-treated patients showed radiologic improvement in osteolysis whereas in the placebo group only 4% improved (P = 0.02 for between-groups comparison). No patient in either group showed worsening of osteolysis. Bone histomorphometry indicated that alendronate tended to normalize turnover indices. There was no evidence of abnormal mineralization in bone biopsies taken from 12 alendronate-treated subjects. The treatment was well tolerated. CONCLUSION: Oral alendronate appears to be a safe and effective therapy for Paget's disease and results in healing of lytic bone lesions.
引用
收藏
页码:341 / 348
页数:8
相关论文
共 24 条
[1]   EFFECTS OF 2 ORAL DOSES OF ALENDRONATE IN THE TREATMENT OF PAGETS-DISEASE OF BONE [J].
ADAMI, S ;
MIAN, M ;
GATTI, P ;
ROSSINI, M ;
ZAMBERLAN, N ;
BERTOLDO, F ;
LOCASCIO, V .
BONE, 1994, 15 (04) :415-417
[2]   TREATMENT OF PAGETS-DISEASE OF BONE WITH INTRAVENOUS 4-AMINO-1-HYDROXYBUTYLIDENE-1,1-BISPHOSPHONATE [J].
ADAMI, S ;
SALVAGNO, G ;
GUARRERA, G ;
MONTESANTI, F ;
GARAVELLI, S ;
ROSINI, S ;
LOCASCIO, V .
CALCIFIED TISSUE INTERNATIONAL, 1986, 39 (04) :226-229
[3]   DURATION OF THE EFFECTS OF INTRAVENOUS ALENDRONATE IN POSTMENOPAUSAL WOMEN AND IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM AND PAGETS-DISEASE OF BONE [J].
ADAMI, S ;
ZAMBERLAN, N ;
MIAN, M ;
DORIZZI, R ;
ROSSINI, M ;
BRAGA, B ;
GATTI, D ;
BERTOLDO, F ;
LOCASCIO, V .
BONE AND MINERAL, 1994, 25 (02) :75-82
[4]   DIPHOSPHONATE THERAPY OF PAGETS-DISEASE OF BONE [J].
CANFIELD, R ;
ROSNER, W ;
SKINNER, J ;
MCWHORTER, J ;
RESNICK, L ;
FELDMAN, F ;
KAMMERMAN, S ;
RYAN, K ;
KUNIGONIS, M ;
BOHNE, W .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1977, 44 (01) :96-106
[5]   TREATMENT OF PAGETS-DISEASE OF BONE [J].
CANTRILL, JA ;
ANDERSON, DC .
CLINICAL ENDOCRINOLOGY, 1990, 32 (04) :507-518
[6]  
CLEELAND CS, 1990, ADV PAIN RES THER, V16, P47
[7]  
DEDEUXCHAISNES CN, 1977, MOL ENDOCRINOL, P513
[8]   RADIOLOGICAL ASSESSMENT OF PAGETS-DISEASE OF BONE AFTER TREATMENT WITH THE BISPHOSPHONATES EHDP AND APD [J].
DODD, GW ;
IBBERTSON, HK ;
FRASER, TRC ;
HOLDAWAY, IM ;
WATTIE, D .
BRITISH JOURNAL OF RADIOLOGY, 1987, 60 (717) :849-860
[9]  
DOYLE FH, 1974, BRIT J RADIOL, V47, P1
[10]   RECONSTRUCTION OF THE RESORPTIVE SITE IN ILIAC TRABECULAR BONE - A KINETIC-MODEL FOR BONE-RESORPTION IN 20 NORMAL INDIVIDUALS [J].
ERIKSEN, EF ;
MELSEN, F ;
MOSEKILDE, L .
METABOLIC BONE DISEASE & RELATED RESEARCH, 1984, 5 (05) :235-242