RANDOMIZED CONTROLLED-STUDY OF EFFECT OF PARATHYROID-HORMONE ON VERTEBRAL-BONE MASS AND FRACTURE INCIDENCE AMONG POSTMENOPAUSAL WOMEN ON ESTROGEN WITH OSTEOPOROSIS

Background Small increases in bone mass are commonly seen with existin g treatments for osteoporosis, which reduce bone remodelling and prima rily prevent bone loss. Since these drugs reduce but do not eliminate risk of fractures, an anabolic agent that would increase bone mass and potentially cure the underlying skeletal problem is needed. Methods W e did a 3-year randomised controlled trial to find out the effects of 1-34 human parathyroid hormone (hPTH [1-34], 400 U/25 mu g daily subcu taneously) in postmenopausal women with osteoporosis taking hormone-re placement therapy (n=17). The controls were women taking hormone-repla cement therapy only (n=17). The primary outcome was bone-mineral densi ty of the lumbar vertebrae, with bone-mineral density at other sites a nd vertebral fractures as secondary endpoints. Findings Patients takin g hormone-replacement therapy and PTH (1-34) had continuous increase i n vertebral bone-mineral density during the 3 years, whereas there was no significant change in the control group. The total increase in ver tebral bone-mineral density was 13.0% (p<0.001); 2.7% at the hip (p=0. 05); and 8.0% in total-body bone mineral (p=0.002). No loss of bone ma ss was found at any skeletal site. Increased bone mass was associated with a reduction in the rate of vertebral fractures, which was signifi cant when fractures were taken as a 15% reduction in vertebral height (p=0.04). During the first 6 months of treatment, serum osteocalcin co ncentration, which reflects bone formation, increased by more than 55% , whereas excretion of crosslinked n-telopeptide, which reflects bone resorption, increased by only 20%, which suggests some uncoupling of b one formation and resorption. By 6 months, there were similar increase s in gradually returned towards baseline progressed. Vertebral bone-mi neral density increased most during the first year of PTH treatment. I nterpretation We found that PTH has a pronouned anabolic effect on the central skeleton in patients on hormone- replacement therapy. PTH als o Increases total-body bone mineral, with no detrimental effects at an y skeletal site. The increased vertebral mass was associated with a re duced rate of vertebral fracture, despite increased bone turnover. Bon e-mass changes may be consistent with a reduction in all osteoporotic fractures. If confirmed in larger studies, these data have important i mplications for the treatment of postmenopausal osteoporosis.