An NIH sponsored study finds that women with osteoporosis showed biochemical evidence of increased bone formation when given Parathyroid Hormone treatment, even after they had been on alendronate (Fosamax) for long periods. A cyclic regimen of parathyroid hormone might be as effective as a daily regimen at increasing bone density of the spine, even when less of the PTH drug is used. Increasing bone density reduces the risk of fractures, which are the major complication of osteoporosis.
The results of the study are reported in the August 11 issue of The New England Journal of Medicine. The principal investigator and lead author of the study is Felicia Cosman M.D., medical director of the Clinical Research Center and osteoporosis specialist at Helen Hayes Hospital in West Haverstraw, New York.
The study evaluated whether patients treated with long-term alendronate, a standard medication for osteoporosis, have a good response to parathyroid hormone treatment. Prior investigations had led to questions about whether these two medications could be used in combination or in sequence. The study also addressed whether short, three-month cycles of parathyroid hormone therapy could be as effective as daily administration. Parathyroid hormone, or PTH, initially stimulates bone formation and later increases the entire bone remodeling process, which includes both degradation and rebuilding of bone. The concept of cyclic administration of parathyroid hormone was based on the hypothesis that early direct stimulation of bone formation by parathyroid hormone might be more important to the ultimate accrual of bone mineral density than later activation of bone remodeling by parathyroid hormone.
Researchers randomly assigned 126 women with osteoporosis who had been taking alendronate for at least one year to daily parathyroid hormone injections, 3-month PTH injections alternating with 3-month periods without parathyroid hormone, or alendronate alone for 15 months. Women in the two PTH groups also stayed on alendronate. The women were recruited at Helen Hayes Hospital and at the Saint Barnabas Osteoporosis Center in Livingston, New Jersey and were given PTH 1-34, which is the same compound currently marketed by Eli Lilly as Forteo.
In both parathyroid hormone groups, markers of bone formation activity rose prominently and rapidly. Among the women, who were receiving cyclic treatment, bone formation declined during cycles without parathyroid hormone and increased again during periods when the medication was administered. Bone breakdown also increased in both PTH groups but increased progressively more in the daily treatment group than in the cyclic-therapy group. The greater ratio of bone building to bone breakdown activity in the cyclic group may explain why the cyclic regimen was as effective as the daily regimen at improving bone density, despite the fact that only 60% of the drug was used in the cyclic regimen.
The data suggest that, after prior and continuing treatment with alendronate, the administration of parathyroid hormone stimulates bone formation and enhances spinal bone mass. “Many women with osteoporosis who have previously been treated with bisphosphonates might benefit from PTH therapy,” states Cosman. “Treatment with PTH should be considered for patients who have previously received alendronate or other bisphosphonates and are still at high risk for fracture.” She suggests that parathyroid hormone may further reduce the incidence of vertebral deformity in patients who have previously been treated with alendronate, although this possibility would need to be confirmed in a larger trial.
The data additionally suggest that intermittent cyclic treatment with PTH produces effects on bone mineral density similar to those induced by daily administration, but at a lower cost and with less effort on the part of patients.
The study did not address the distinct clinical issue of concomitant treatment with PTH and alendronate in patients who have never been treated for osteoporosis. That is the subject of a companion article in the same issue of The New England Journal of Medicine. That article indicates that for women, who have not been on bisphosphonate medications previously, the use of PTH followed by alendronate may be the most effective bone building sequence.
PTH 1-34 is the first bone-building drug to be used to treat osteoporosis, and is currently approved as Forteo for use for up to two years in postmenopausal women and men at high risk of osteoporosis related fracture.
This study was sponsored by the National Institute of Arthritis, Musculoskeletal and Skin Disorders, part of the NIH. Other investigators of the study were Jeri Nieves, PhD., Marsha Zion, M.S., Lillian Woelfert, R.N., and Robert Lindsay, M.D., all with the Clinical Research Center at Helen Hayes Hospital, and Marjorie Luckey, M.D. from St. Barnabas Osteoporosis Center in Livingston, NJ.
For additional information about osteoporosis, visit the website of the New York State Osteoporosis Prevention and Education Program at www.nysopep.org.