Hotline Archive - Alendronate (Fosamax) Trials in Osteoporosis
October 1995
Bankhurst, A. et al reported in an abstract, "Three-year Treatment with Alendronate Prevents Fractures in Women with Postmenopausal Osteoporosis," (to be presented at the ACR National Scientific Meeting in San Francisco) that alendronate produces highly significant increases in bone mineral density (BMD) of the spine, femoral neck, and total body.
Alendronate sodium (ALN), an aminobisphosphonate, is a potent, selective inhibitor of bone resporption which has been shown to be effective in the treatment of osteoporosis. The two Primary Phase III Studies of identical design randomized 994 postmenopausal women (approximately 500 per study) with osteoporosis (spine BMD > 2.5 SD below peak) to ALN 5 or 10 mg/d for three years, or 20 mg/d for two years and 5 mg/d for the 3rd year or double blind placebo (PBO). All received 500 mg of calcium per day. Spine films were done to measure vertebral fractures (VFxs) and vertebral deformity. Statue was measured every 3-6 months.
ALN was well tolerated. All doses induced highly significant BMD increases in the spine, femoral neck, and total body. Ten mg/d ALN was maximally effective. Twenty percent of the patients had VFxs at baseline. Of the 881 evaluable patients, 6.2 percent on PBO and 3.2 percent on ALN had one or more new VFxs (p=0.034) . Of the patients with new VFxs, 68 percent of PBO and 18 percent of ALN treated patients had two or more VFxs. The ALN group had significantly fewer total VFxs (4.2 to 11.3 per 100 patients). The spinal deformity index favored the ALN group with significant reduction in statue loss compared to PBO. PBO and ALN treated patients with at least one new VFx lost a mean 23.3 mm and 5.9 mm in height respectively.
This report concluded that ALN produces a highly significant increase in BMD in spine, hip, and total body that are progressive over three years of treatment. ALN induced highly consistent, statistically significant, and clinically important reductions in vertebral and nonvertebral fractures, vertebral deformity, and loss of statue.
Emkey, R., et al in a second abstract, "Progressiveness and Generalizability of the Effects of Alendronate on Bone Mass and Safety Experience in Postmenopausal Women with Osteoporosis," reported on the time course of the effects of oral ALN on BMD and the impact of various patient characteristics on response and tolerability from the combined data from the two Primary Phase III
Studies of identical design. The data showed that the PBO lost from .7-1.2 percent BMD over the 36 month study period. The ALN group showed a marked and progressive increase in BMD at month 36 of 8.8 percent, 5.9 percent, and 7.8 percent at the spine, femoral neck, and trochanter respectively. Similar results were seen with the 20/5 mg ALN group, whereas ALN 5 mg
was significantly less effective than the 10 mg at all sites. At each dose, similar efficacy was seen regardless of concomitant medication, renal function, initial bone turnover rate, race, and age.
Alendronate is one of several new bisphosphonates being studied for treatment of postmenopausal osteoporosis. Alendronate has been approved by the FDA. Considerable media attention will be focused on these drugs over the next several months. These drugs will enhance our ability to treat postmenopausal osteoporosis more effectively.
Prepared by Robert Thoburn, MD, and Paul Katz, MD, editors.
October 4, 1995
This Hotline is provided by the American College of Rheumatology Communications and Marketing Group as an information service for members. This Hotline does not represent a position statement of the College.
