A RANDOMIZED CONTROLLED TRIAL TO COMPARE THE EFFICACY OF CYCLICAL PARATHYROID-HORMONE VERSUS CYCLICAL PARATHYROID-HORMONE AND SEQUENTIAL CALCITONIN TO IMPROVE BONE MASS IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS

Short cycles of human(h) PTH-(1-34) may have an anabolic effect to inc rease bone mass in patients with osteoporosis. As PTH also stimulates bone resorption, it is theoretically possible to enhance the anabolic effects of PTH by using a sequential antiresorptive agent in the treat ment cycle. To test this hypothesis, 30 women with osteoporosis, aged 67 +/- 8 yr, completed a 2-yr protocol that comprised 28-day courses o f hPTH-(1-34) (800 U) given by daily sc injections; each course was re peated at 3-month intervals. By random allocation, patients either rec eived sequential calcitonin (CT) immediately following the cycle of hP TH-(1-34) (75 U/day, sc; PTH+CT; n = 16) or placebo CT (PTH alone; n = 14) for 42 days. Baseline bone mineral density (BMD) at the lumbar sp ine site revealed t scores of -3.7 +/- 1.2 (+/-SD) for the PTH alone g roup and -3.0 +/- 1.4 for the PTH+CT groups, who had 2.0 +/- 2.3 and 1 .8 +/- 2.4 vertebral fractures, respectively, at entry to the study. A t the end of the 2 yr, the lumbar spine BMD increased from 0.720 +/- 0 .130 to 0.793 +/- 0.177 g/cm(2) (10.2%) in the PTH group and from 0.76 0 +/- 0.168 to 0.820 +/- 0.149 g/cm(2) (7.9%) in the PTH+CT group. The se changes were significant over time in both groups (P < 0.001). Alth ough the final 2-yr lumbar spine BMD was not signifi cantly different between the two treatment groups, those patients receiving sequential CT injections gained bone mass at a consistently slower rate. Changes in BMD at the femoral neck averaged +2.4% and -1.8% in the PTH and PTH +CT groups, respectively, neither of which was significant. In the gro up receiving only cyclical hPTH-(1-34), the observed 2-yr vertebral fr acture incidence was 4.5 compared to 23.0/100 patient yr in the PTH+CT group (P = 0.078). During the first two cycles, changes in biochemica l markers of bone formation (serum total alkaline phosphatase, bone-sp ecific alkaline phosphatase; and osteocalcin) and bone resorption (fas ting urinary hydroxyproline and N-telopeptide excretion) were signific antly increased over pretreatment values after 28 days of hPTH-(1-34) injections (P < 0.05 to P < 0.01 for both groups). Even end of cycle v alues remained elevated over the study baseline across time (P < 0.01) . There were no significant differences for any outcome parameter betw een the two treatment groups. We conclude that short cycles (28 days) of daily hPTH-(1-34) injections result in significant increases in lum bar spine BMD, without significant changes in cortical bone mass at th e femoral neck. Very low incident vertebral fracture rates were docume nted over 2 yr. However, there is no evidence that sequential antireso rptive therapy with CT is of any benefit over that conferred by cyclic al PTH alone.