ALENDRONATE DOES NOT BLOCK THE ANABOLIC EFFECT OF PTH IN POSTMENOPAUSAL OSTEOPOROTIC WOMEN

In rodent osteoporosis models, anabolic activity of parathyroid hormon e (PTH) is preserved in the presence of antiresorptive agents, Anaboli c activity is also preserved when PTH is administered to estrogenized postmenopausal women, In contrast, in the ewe treated with tiludronate , PTH-induced stimulation of bone turnover did not occur. To determine whether PTH in combination with alendronate could be a viable treatme nt for osteoporosis, we performed a short-term study of postmenopausal women with osteoporosis (n = 10) already on alendronate 10 mg/day to determine whether PTH could increase bone formation assessed biochemic ally, Patients continued alendronate alone (n = 5) or continued alendr onate with 400 IU/day subcutaneous human PTH(1-34) added for 6 weeks. Subjects receiving PTH had serum and urine sampling weekly during PTH treatment and for 5 weeks thereafter, Sampling was performed approxima tely biweekly for subjects who had been on alendronate alone for 11 we eks, Samples were analyzed for osteocalcin (OC), propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase (BSAP), cross-l inked urinary N-telopeptide (NTX), and free urinary pyridinoline (PYD) , Markers of bone formation increased within 3 weeks in the PTH plus a lendronate group, with mean peak levels at 5-7 weeks: OC 49%, p < 0.01 ; PICP 61%, p < 0.01; and BSAP 24%, p = 0.12. Levels returned to basel ine after discontinuing PTH, with PICP declining the most rapidly. The re were no significant changes at any time in the alendronate alone gr oup. There were no increments in either urinary NTX or PYD in either t reatment group throughout the observation period. The bone turnover ma rker changes seen with PTH plus alendronate were similar to those seen with PTH plus hormone replacement. These data suggest that: PTH can s timulate bone formation, evidenced by elevations of bone formation mar kers, even in the presence of a potent bisphosphonate; in the presence of alendronate, PTH-stimulated bone formation precedes stimulation of bone resorption, suggesting that PTH stimulates bone formation de nov o; and the combination of PTH and alendronate may be a viable treatmen t option for postmenopausal women with osteoporosis.