SAN DIEGO – Teriparatide is gaining traction as an off-label therapy to speed fracture repair and promote healing of delayed union and nonunion fractures.
At a session expressly devoted to anabolic agents for fracture repair at the annual meeting of the American Society for Bone and Mineral Research, Dr. Robert Marcus said he is aware of numerous anecdotal reports of successful use of teriparatide (Forteo) to accelerate fracture healing and shorten return-to-play time in high-profile professional and elite collegiate athletes.
Although HIPAA regulations prevent him from naming any of the American athletes involved, Dr. Marcus said, HIPAA doesn't apply to the Italian soccer superstar Francesco Totti.
Totti, a prolific goal scorer known as Il Bimbo d’Oro (The Golden Boy) and Il Gladiatore, suffered a serious combined tibia/fibula fracture in the spring of 2006. The injury was expected to keep him out of action for the entire World Cup tournament that summer, and for well beyond. But he was placed on teriparatide almost immediately after the fracture. He played every game of the series, Italy won the 2006 World Cup, and Totti was named to the tournament’s all-star team.
Dr. Marcus, professor of medicine emeritus at Stanford (Calif.) University and a former Eli Lilly employee, made it clear he is not promoting the off-label use of teriparatide to accelerate fracture healing. He recalled that when Eli Lilly approached the Food and Drug Administration with the aim of gaining this additional indication, the agency required as an initial proof-of-concept study a randomized, double-blind, placebo-controlled trial conducted in postmenopausal women with a distal radial fracture incurred within the previous 10 days.
That multicenter study in 102 women with Colles’ fracture showed a highly significantly shorter time to healing with 8 weeks of daily teriparatide at the standard 20-mcg dose used for osteoporosis therapy than with placebo, although the 40-mcg dose unexpectedly proved ineffective (J. Bone Miner. Res. 2010;25:404-14).
But Colles’ fracture isn’t really a good test of the therapy, according to Dr. Marcus, because it doesn’t involve weight-bearing bones. Where an agent for acceleration of fracture repair would really be a boon in young people with, say, tibia fractures caused by motorcycle or skateboarding accidents. Such fractures often fail to heal successfully with conservative treatment in a reasonable time and eventually require surgical fixation and metal hardware, the endocrinologist said.
Dr. Marcus noted that Dr. Susan V. Bukata, an orthopedic oncologist at the University of Rochester (N.Y.), has previously reported on 145 patients with painful delayed/nonunion fractures treated with daily teriparatide at the standard 20-mcg dose. Within 12 weeks of starting therapy, 93% of patients in this retrospective observational series showed full radiographic and clinical healing. Another 4% had partial radiographic union that functioned clinically as a healed fracture. Only 3% of patients remained unimproved after 12 weeks of teriparatide. Dr. Bukata’s series has grown to more than 500 patients treated for delayed/nonunion fractures; the data are now being analyzed.
In order to gain an FDA indication for acceleration of fracture healing, however, it will be essential to conduct a randomized controlled trial involving fractures at clinically appropriate sites. Quantitative assessment of radiographic endpoints with CT and/or MRI will be a must, as will inclusion of functional end points such as pain reduction, muscle strength, ambulation, and return to work or daily activities. The FDA’s concern about osteosarcomas and other bone tumors seen in rats on lifelong very-high-dose teriparatide will be an issue, Dr. Marcus predicted.
Elsewhere at the meeting, Dr. Peter Peichl presented a study that fulfilled many of the requirements of a pivotal trial, albeit using the naturally occurring parathyroid hormone (PTH) containing 84 amino acids rather than its close relative, teriparatide.
The study involved 65 elderly postmenopausal women hospitalized for painful pubic bone fractures to be treated without surgery. In all, 21 patients were randomized to once-daily injection of 100 mcg of PTH. The 44 women who didn’t receive PTH served as controls. All participants received daily calcium and vitamin D supplements.
The 21 patients in the PTH-treated group showed CT-confirmed healing of their pubic bone fractures at a mean of 7.8 weeks, significantly faster than the 12.6 weeks in controls. At 8 weeks, all subjects in the PTH study arm were healed, as were only 4 of 44 controls. In addition, the PTH-treated patients showed bigger and faster improvements on a pain visual analog scale and on the Timed Up and Go functional assessment, reported Dr. Peichl of Evangelical Hospital Vienna.
Dr. Peichl declared having no financial conflicts. Dr. Marcus is a consultant to and on the speaker’s bureau for Eli Lilly.