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Risedronate or Alendronate affects treatment with Teriparatide?
Urdinola Jaime MD
CS AK 9 116-20 326 - Medical Association of the Andes - Bogotá DC Colombia
Urdinola Jaime MD
CS AK 9 116-20 326 - Medical Association of the Andes - Bogotá DC Colombia
Phone: 571 / 215 23 00 - Phone: 57 / 315 236 e August 28
Symposium / Luncheon on Menopause - Wednesday, February 25, 2009 1st Floor Boardroom Medical Association Andes - AK 9 116-20 Bogotá DC Colombia
Introduction has been shown that teriparatide, human PTH (1-34), reduces the risk of new vertebral and nonvertebral fractures in postmenopausal women with osteoporosis 1.
As the use of teriparatide is recommended only for 18 to 24 months, patients with large and early response are those that present the optimum benefit of the anabolic agent. Also is known that pretreatment with antiresorptive as estrogen and raloxifene allows teriparatide rapidly increase bone turnover markers and bone mineral density (BMD), whereas treatment with alendronate before administration of teriparatide or in combination with this can disrupt or delay the response 2. This could be explained, considering that alendronate remains as reported, for longer in the bone due to its greater affinity for hydroxyapatite.
combined or sequential studies with bisphosphonates and teriparatide are used almost exclusively alendronate. Therefore, until not yet known whether other bisphosphonates can disrupt or delay the anabolic response to teriparatide, an effect that may be related to the extent to which the bisphosphonate reduces bone turnover and maintains this reduction after stopping the drug.
Based on the pharmacological differences between alendronate and risedronate, the authors of the study that analyzes today postulate the hypothesis that risedronate might not affect the after-effects of teriparatide in the same magnitude as previous treatment with alendronate. This study in 324 postmenopausal women with osteoporosis is clinically relevant, as many patients receiving teriparatide have been treated con uno de estos dos bisfosfonatos.
Métodos
Pacientes que habían sido tratadas previamente con alendronato o Risedronato durante por lo menos 24 meses, descontinuaron el bisfosfonato y recibieron teriparatida durante 12 meses. En un estudio multinacional y de grupos paralelos, de acuerdo con las guías de buenas prácticas clínicas, la Declaración de Helsinki y las normas de diferentes países que participaron en el estudio 3 .
Patrocinadores
El estudio fue diseñado por el Comité Directivo de los Investigadores y la Alianza para la Mejor Salud Ósea (Procter&Gamble Pharmaceuticals y Sanofi-aventis).
Researchers in each country collected the data, the Sanofi-aventis statistical data analyzed according to an agreed plan and pre-specified by the sponsors. All authors had full access to the raw data, wrote the manuscript and are responsible for the accuracy and complete publication.
also was conducted independent statistical review at Helen Hayes Hospital in New York, under the guidance of the Steering Committee Investigators. The findings of this independent statistical review agreed with those of the original statistical analysis.
Study Population We included postmenopausal women with osteoporosis who received alendronate or risedronate for at least 24 months (lumbar spine or total hip, index < 2.0
T (<> 1, levels of 25-OH-vitamin D
> 16 and < 80 ng/ml, telopéptido urinario (NTX) < 50 equivalentes de colágeno óseo nmol/mmol de creatinina, para asegurar la adherencia a la terapia previa con bisfosfonatos.
Excluded those with decreased renal function, treatment with other antiresorptive different risedronate or alendronate, hormone therapy with sex steroids in the previous 36 months, systemic corticosteroids or anabolic in the previous 3 months for 1 month or for longer than in the previous 6 months, calcitonin, calcifediol calcitriol or the month before or during a longer period in the previous 6 months, a combination of risedronate and alendronate previous 60 months, or any antiresorptive agent in combination with risedronate or alendronate.
Study Protocol After the recruitment of patients discontinued their bisphosphonate and started daily teriparatide (20 mcg SC) for 12 months, controlled 11 times. Because the study was open and nonrandomized, were pooled and stratified according to the bisphosphonate received. Outcomes
The primary endpoint of analysis was to compare the mean absolute change from baseline of the N-teminal peptide (P1NP) after 3 months of treatment with teriparatide, among subjects who had previously received Risedronate and alendronate. This time of 3 months was selected by previous reports of associations between early changes in bone turnover markers with BMD improved to 12-18 and 24 months.
analysis The secondary endpoints included comparisons with the baseline of the average changes and relationship to P1NP (N-terminal propeptide of collagen type 1), the activity of bone-specific alkaline phosphatase (BAP), osteocalcin (OC ), serum C-telopeptide (CTX) and the ratio of N-telopeptide with urinary creatinine (NTX) at 0.5, 1-6 and 12 months.
also included comparisons of average and percentage changes in area de la DMO por DXA a los 6 y 12 meses, así como la DMO volumétrica por tomografía computadorizada en forma basal y a los 12 meses.
Se investigaron las correlaciones de los cambios tempranos en los marcadores óseos con los cambios en la DMO a los 12 meses.
Resultados
En el grupo que previamente había recibido Risedronato, el aumento de P1NP fue significativamente mayor después de 3 meses de tratamiento con teriparatida que en el grupo que había recibido alendronato ( promedio + SE [Error estándar] 86.0 + 5.6 vs. 61.2 + 5.3 ng/mL, respectivamente; P < 0.001).
Los hallazgos fueron similares para los otros marcadores de recambio óseo.
Los cambios en el BMD area and volumetric analysis of the trabeculae of the vertebrae were higher in the group who had previously received risedronate (P <0.05).
Early changes in bone turnover markers were correlated with BMD changes in the volumetric analysis the trabeculae of the vertebrae at 12 months (Spearman r = 0.45), finding that after treatment with risedronate, changes at 12 months were almost twice that observed in the alendronate group.
treatment Teriparatide was well tolerated in both groups. The most frequently reported adverse effects were hypercalcemia, muscle spasms, nausea, dizziness and arthralgia.
Conclusions
This nonrandomized but prospective study suggests that there may be differences in anabolic response to teriparatide as a function of prior exposure to the type of bisphosphonate. The patients previously treated with risedronate showed a greater response with early and pronounced increase in levels of P1NP level and volumetric BMD, than those previously treated with alendronate. This requires further investigation to fully understand the potential clinical impact.
The study was designed using teriparatide for 12 months. Was not powerful enough to measure the incidence of fractures and should be considered in this context.
References
1 - Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001, 344: 1434-1441.
2 - Black DM, Greenspan SL, Ensrud Ker, Palermo L, McGowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JPO, Rosen CJ, PATH Study Investigator. The effect of parathyroid hormone and alendronate Alone or in combination in postmenopausal osteoporosis. N Engl J Med 2003; 349: 1207 – 1215.
3- Miller PD, Delmas PD, Lindsay R, Watts NB, Luckey M, Adachi J, Saag K, Greenspan L, Seeman E, Boonen S, Meeves S, Lang TF, Bilezikian J, for the Open-label Study to Determine How Prior Therapy with Alendronate or Risedronate in Postmenopausal Women with Osteoporosis Influences the Clinical Efectiveness of Teriparatide Investigators. Early Responsiveness of Women with Osteoporosis to Teriparatide After Therapy with Alendronate or Risedronate. J. Clin Endocrinol Metab 2 008; 93: 3785-3793.
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