THERAPY WITH ZOLEDRONIC ACID IN OSTEOPOROTIC POSMENOPAUSAL WOMEN María Torrea1, Miguel Artacho1, Cristina Díez1, Itxasne Cabezón1, Paloma Díez1, Maria Olmedo1, Chiara Fanciulli1, José Santiago Filgueira1. 1.-Internal Medicine III. Hospital General Universitario Gregorio Marañón (Madrid).
INTRODUCTION: Zoledronic Acid is an intravenous biphosphonate that inhibits bone resorption mediated by osteoclasts. ZA has proven efficacy in secondary prevention of osteoporosis by reducing the onset of subsequent osteoporotic related fractures as well as optimization of bone marrow density(BMD). ZA has reported adverse effects: muscular ache, fever, headache, and as important ones renal insufficiency, atrial fibrilation, and cerebral or cardiovascular ischemic events.
AIM: Evaluate the changes in serum concentrations of bone metabolism biomarkers (PTH), as well as reported adverse effects; comparing first and second subsequent dose of ZA regarding adaptation of BMD to referred treatment.
MATERIAL AND METHODS: •A prospective cohort observational study of46 post-menopausal osteoporotic women •2 consecutive annual doses of ZA •Baseline and first month follow-up mesearues: calcium, phosphate, f. alcaline, vit D, PTH, calcium and creatinine in urine •Adverse effects reported. •SPSS 15.5. t-Student related samples and Wilcoxon correlation for non parametric
RESULTS •8 losts (1 éxitus non related with the drogue, 7 losts) • No significative statistical differences were found in values of calcium, phosphate, f.alcaline, vit D between the infusions. • Higher alterations related to urine calcium between the 1st and the 2nd dose: Ca urine: p= 0,028 • Not seen between basal value and the 1st infusion, neither between basal value and the 2nd infusion. Respectively: Ca urine: p=0,356, y p=0,799 •Differences were objectived between PTH basal and the 1st infusion (p=0,01). But not between PTH basal and the 2nd infusion(p=0,589) • Adverse effects: minimally higher after the 1st infusion. Not after the 2nd one. MAINLY Pirexy 9,5% Muscular ache 7,5% Headache 10% No case of renal insufficiency, not even atrial fibrilation
Values between basal and 2nd infusion
Ca_2 - Ca_0 Z
-,472(a)
Sig. asintót. (bilateral)
,637
P_2 - P_0 -,207(b) ,836
SECUNDARY EFFECTS
Headache Pirexy Muscular ache
Values between basal and 1st infusion FAlc_2 FAlc_0 -2,530(b) ,011
PTH_2 - PTH_0 -,540(a) ,589
VitD_2 - VitD_0 -1,189(a) ,234
Cao_2 - Cao_0 -,255(a) ,799
Creatorina_2 Creatorina_0 -1,680(b) ,093
Ca_1 Ca_0 Z Sig. asintót. (bilateral)
P_1 - P_0
FAlc_1 FAlc_0
Values between 1st and 2nd infusion PTH_1 PTH_0
VitD_1 VitD_0
Cao_1 Cao_0
Creato_1 - DMOL_1 - DOMF_1 Creatorina_0 DMOL_0 DOMF_0
-,229(a)
-1,539(a)
-3,083(a)
-3,382(b)
-1,092(b)
-,923(a)
-,517(b)
-,948(a)
-,736(b)
,819
,124
,002
,001
,275
,356
,605
,343
,461
Ca_2 - Ca_1 Z Sig. asintót. (bilateral)
P_2 - P_1
FAlc_2 FAlc_1
Creatorina_2 PTH_2 - PTH_1 VitD_2 - VitD_1 Cao_2 - Cao_1 Creato_1
-,228(a)
-,541(a)
-1,447(b)
-1,100(b)
-,227(b)
-2,193(b)
-2,191(b)
,820
,589
,148
,271
,820
,028
,028
CONCLUSSION: As conclusions: The significative increase in PTH values after the 1st infusion of Zoledronic acid could be related with the higher number of adverse effects, which does not happen after the 2nd dose. These changes could be due to a higher imbalance in bone homeostasis at the beggining of the treatment, until the bone reaches a balance and a better adaptation to the treatment.
BIBLIOGRAPHY: D.M. Black and Others Acido zoledrónico una vez al año para el tratamiento de la osteoporosis postmenopáusica. NEJM Mayo 2003, 1809-1823. K.W. Lyles and Others. Acido zoledrónico, frascturas clínicas y mortalidad tras una fractura de cadera. NEJM, Nov 2007: 1799-1810 K Saag et al. Una sola perfusión de acido zoledrónico reduce los marcadores de resorción ósea más rápidamente que alendronato oral semanal en mujeres postmenopáusicas con densidad mineral ósea baja. BONE Mayo 2007, Vol 40, Num 5
