Analysis shows Teriparatide reduces fracture risk independent of bone turnover

Oct 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.

Forteo (teriparatide [rDNA origin] injection), 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.

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.