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Analysis Showed Teriparatide Reduced Fracture Risk Independent of Bone Turnover: Presented at ASBMR

SEATTLE, WA -- October 5, 2004 -- Data presented yesterday at the 26th annual meeting of the American Society for Bone and Mineral Research (ASBMR) show that the ability of teriparatide to prevent fractures remained consistent regardless of pretreatment bone turnover status. Bone is living tissue that constantly regenerates itself by breaking down and reforming, a process referred to as bone turnover. Osteoporosis can occur when bone break down exceeds bone formation.

"In most cases, rapid bone turnover can be dangerous and lead to fracture in osteoporotic patients," said the study's primary investigator, Pierre Delmas, MD, Claude Bernard University of Lyon, France. "In this study, regardless of whether patients had high turnover rates before being treated, we saw a reduced risk of fractures with teriparatide."

This post-hoc analysis examined biochemical markers of bone turnover, which provide information about the rate of bone turnover. This rate can vary considerably in postmenopausal women with osteoporosis. In this study, the impact of the pretreatment bone turnover rate on the response to teriparatide was examined.

ForteoŽ (teriparatide [rDNA origin] injection), the first and only bone formation agent approved for the treatment of osteoporosis, was granted FDA approval in November 2002. It stimulates new bone formation by increasing the number and activity of bone forming cells called osteoblasts. Forteo is approved for the treatment of osteoporosis in postmenopausal women who are at high risk for fracture and to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. These include men (and postmenopausal women) with a history of osteoporosis-related fracture, or who have multiple risk factors for fracture, or who have failed or are intolerant to previous osteoporosis therapy, based upon physician assessment.

Until Forteo's approval, the only approved osteoporosis treatments were antiresorptives, which work mainly to slow or stop bone loss by reducing the number and action of bone-removing cells called osteoclasts.

About the Analysis

To determine whether rate of bone turnover affects teriparatide's effect, this analysis looked at the relationship between baseline biochemical markers of bone turnover and the ability of teriparatide to reduce the occurrence of fractures.

Five biochemical markers from postmenopausal women with osteoporosis who participated in the pivotal Forteo Fracture Prevention Trial were analyzed.

The Fracture Prevention Trial (FPT), a registration trial for Forteo, was a randomized, double-blinded, placebo controlled study that enrolled 1,637 women with osteoporosis. Subjects were randomized to teriparatide 20 mcg/day (marketed as Forteo), teriparatide 40 mcg/day or placebo for a median of 19 months.

A subset of 520 women had biochemical markers of bone turnover (serum bone-specific alkaline phosphatase [BSAP], serum carboxy-terminal extension peptide of procollagen type 1 [PICP], urinary N-terminal telopeptide [NTX], and urinary free deoxypyridinoline [DPD]) measured at baseline. A partially overlapping subset of 771 women also had serum amino-terminal extension of peptide of procollagen type 1 [PINP] evaluated at baseline. BSAP, PICP and PINP are all markers of bone formation, whereas DPD and NTX are markers of bone resorption.

Analysis found that subjects with higher baseline concentrations of BSAP, PINP, NTX and DPD had a higher risk of a new fragility fracture. Teriparatide significantly reduced the risk of vertebral and nonvertebral fragility fractures regardless of pretreatment bone turnover, according to study results.

Important Safety Information about Forteo

In two-year studies in rats, teriparatide caused an increase in the incidence of osteosarcoma, a malignant bone tumor, which was dependent on dose and duration of treatment. Although no case of osteosarcoma has been reported in the patients who received Forteo in clinical trials, it is not known if humans treated with Forteo are at increased risk for this cancer.

Forteo should be prescribed only to patients for whom the potential benefits are considered to outweigh the potential risk. The drug should not be prescribed for patients at increased baseline risk for osteosarcoma, including patients with Paget's disease of bone or unexplained elevations of alkaline phosphatase, children or growing adults, or those who have had prior external beam or implant radiation therapy involving the skeleton.

Additionally, patients with bone metastases or a history of skeletal malignancies, and those with metabolic bone diseases other than osteoporosis, should not receive Forteo. Patients with high levels of calcium in their blood should not receive Forteo due to the possibility of increasing their blood levels of calcium. In clinical trials, the most frequent treatment-related adverse events reported at the 20-microgram (mcg) dose approved for marketing were mild, similar to placebo and generally did not require discontinuation of therapy. Reported adverse events that appeared to be increased by Forteo treatment were leg cramps and dizziness (2.6 and 8 percent, respectively), compared with placebo (1.3 percent and 5.4 percent, respectively).

Forteo is supplied in a disposable pen device that can be used for up to 28 days to give once-daily self-administered injections. Forteo is available in a 20-mcg dose and should be taken for a period of up to 24 months. Lilly has implemented a risk management program that includes comprehensive measures regarding the appropriate use of Forteo in the target patient population. A Medication Guide explaining the details of the drug to the patient also accompanies the product. Forteo also has a black box warning in its package insert about the osteosarcoma findings in rats during preclinical testing. For full prescribing information, please visit http://www.forteo.com.

About Osteoporosis

More than 50 percent of all women over the age of 75 are estimated to have osteoporosis, and due to their advanced age, have a high risk of fracture. In fact, most American women over the age of 50 will experience one or more osteoporosis-related fractures during their lifetimes, and women with osteoporosis who have two or more previous fractures have up to a nine times greater risk of future fracture compared with women who have not suffered a previous fracture.


SOURCE: Eli Lilly and Company

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