Eli Lilly and Company presented data comparing the mechanisms of action of Forteo (teriparatide [rDNA origin] injection) and zoledronic acid based on data that evaluated histomorphometric measurements of bone remodeling in transiliac crest bone biopsies from postmenopausal women with osteoporosis. These data were presented in an oral presentation at the 2011 Annual Meeting of the American Society for Bone and Mineral Research (ASBMR) in San Diego, California.
Dynamic indices of bone formation, including mineralizing surface/bone surface (MS/BS) and bone formation rate (BFR), were significantly higher in women treated with Forteo than in women treated with zoledronic acid at six months.
"What makes this study important is that it was through the use of a complete panel of bone biopsy indices that we confirmed the differences in the mechanism of action of the two osteoporosis treatments," said David W. Dempster, PhD, professor of clinical pathology, Columbia University.
The study's primary objective was to compare the effects of Forteo or zoledronic acid on MS/BS at six months. MS/BS is a measure of the proportion of bone surface upon which newly mineralized bone is being deposited. Results showed that in women treated with Forteo, MS/BS was significantly higher than in those treated with zoledronic acid (median: 5.60 per cent vs. 0.16 per cent; p<0.001).
Secondary outcomes demonstrated: a significantly greater increase in BFR/BS (bone formation rate/bone surface) in patients taking Forteo (median: 0.0116 mm3/mm2/y) compared to those taking zoledronic acid (median: 0.0009 mm3/mm2/y) (p<0.001) (double-labels only); a significantly greater increase in mineral apposition rate (MAR) in patients taking Forteo (median: 0.56 µm/d) compared to those taking zoledronic acid (median: 0.50 µm/d) (p=0.03) (double-labels only); increased serum markers of bone formation and resorption (P1NP, OC and CTX) with Forteo; zoledronic acid decreased these markers; and adverse event profiles for both drugs that were similar to those reported previously and contained within the product labelling.
"We believe that these data make an important contribution to the body of evidence supporting the mechanism of action for Forteo," said Kathleen Taylor, PhD, Eli Lilly and Company.
Forteo is used in both men and postmenopausal women with osteoporosis who are at high risk for having broken bones (fractures). Forteo is used in both men and women with osteoporosis due to use of glucocorticoid medicines, such as prednisone, for several months, who are at high risk for having broken bones (fractures). Forteo can be used by people who have had a fracture related to osteoporosis, or who have several risk factors for fracture, or who cannot use other osteoporosis treatments.
During the drug testing process, the medicine in Forteo caused some rats to develop osteosarcoma, which, in humans, is a serious but rare bone cancer. Osteosarcoma has been reported rarely in people who took Forteo, and it is unknown if people who take Forteo have a higher chance of getting the disease. Before patients take Forteo, patients should tell their healthcare provider if they have Paget's disease of bone, are a child or young adult whose bones are still growing or have had radiation therapy.
"Skeletal Histomorphometry in Patients On Teriparatide or Zoledronic Acid Therapy (SHOTZ) Study: 6-Month Results of a Randomized Clinical Trial" was a six-month, randomized, double-blind, cross-sectional biopsy study that compared histomorphometric parameters of bone remodeling in 58 postmenopausal women with osteoporosis. Participants received either 20 µg/d teriparatide (TPTD, n=28) or 5 mg/y zoledronic acid (ZOL, n=30).
The study's primary endpoint was the comparison of mineralizing surface/bone surface (MS/BS) between treatment groups, assessed by bone histomorphometry in cancellous compartment of iliac crest bone biopsy at month six (obtained after double tetracycline labeling). Secondary endpoints included comparison of bone formation rate (BFR/BS), mineral apposition rate (MAR) and other standard histomorphometric indices in iliac crest bone biopsies at six months; change from baseline to months one, three and six in biochemical markers of bone turnover; and safety evaluations of vital signs, laboratory analyses, pre-biopsy assessments and treatment-related adverse events.
Participants aged 55 to 89 years were enrolled based on bone mineral density (BMD) and fracture criteria as assessed by the investigators.
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