A phase 2 study of MK-5442, a calcium-sensing receptor antagonist, in postmenopausal women with osteoporosis after long-term use of oral bisphosphonates.
Osteoporos Int
; 27(1): 377-86, 2016 Jan.
Article
en En
| MEDLINE
| ID: mdl-26556736
ABSTRACT
UNLABELLED In women with osteoporosis treated with alendronate for >12 months and oral bisphosphonates for >3 of the last 4 years, switching to MK-5442, a calcium receptor antagonist, stimulated endogenous parathyroid hormone (PTH) secretion and increased bone turnover marker levels, but produced a decline in bone mineral density (BMD) at all sites. INTRODUCTION:
This study assessed the effects of switching from long-term oral bisphosphonate therapy to the calcium-sensing receptor antagonist MK-5442 on BMD and bone turnover markers (BTMs) in post-menopausal women with osteoporosis.METHODS:
This randomized, active and placebo-controlled, dose-ranging study enrolled 526 postmenopausal women, who had taken alendronate (ALN) for ≥12 months preceding the trial and any oral bisphosphonate for ≥3 of the preceding 4 years and had spine or hip BMD T-scores ≤-2.5 or ≤-1.5 with ≥1 prior fragility fracture. Women were randomized to continue ALN 70 mg weekly or switch to MK-5442 (5, 7.5, 10, or 15 mg daily) or placebo.RESULTS:
Switching from ALN to MK-5442 produced a dose-dependent parathyroid hormone (PTH) pulse of threefold to sixfold above baseline at 1 h, with PTH levels that remained twofold to threefold above baseline at 4 h and returned to baseline by 24 h. Switching to MK-5442 or placebo increased BTM levels compared to baseline within 3 months and MK-5442 10 mg increased BTM levels compared to placebo by 6 months. With all MK-5442 doses and placebo, spine and hip BMD declined from baseline, and at 12 months, BMD levels were below those who continued ALN (all groups P < 0.05 vs ALN). There was also a dose-dependent increase in the incidence of hypercalcemia with MK-5442.CONCLUSION:
Switching from ALN to MK-5442 resulted in a pulsatile increase in PTH and increases in BTMs, but a decline in BMD compared with continued ALN. MK-5442 is not a viable option for the treatment of osteoporosis.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Propanolaminas
/
Benzoatos
/
Osteoporosis Posmenopáusica
/
Difosfonatos
/
Conservadores de la Densidad Ósea
Tipo de estudio:
Clinical_trials
Límite:
Aged
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Osteoporos Int
Asunto de la revista:
METABOLISMO
/
ORTOPEDIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos