PTH for osteoporosis: weekly injection instead of daily?

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Sep 23, 2002

PTH for osteoporosis: weekly injection instead of daily?

San TX Parathyroid hormone (PTH) for osteoporosis continues to

occupy a prominent place in research even though clinicians have yet to get

their hands on this therapeutic option. Teriparatide (Forteo®, Lilly) is the

closest to market, having been recommended for approval by an FDA advisory

committee last year, but it has yet to be launched rumors are circulating

that there are problems with manufacture.

PTH has aroused such interest because of its impressive results in fracture

reduction greater than have been seen with other therapies. But these

results were achieved with once-daily subcutaneous injections, leading to

concerns over compliance and also over the cost of the therapy. Now comes

the suggestion that once-weekly injections may offer the same therapeutic

effect.

The suggestion was made by Dr Dennis Black (University of California San

Francisco) and Dr Clifford Rosen (Maine Center for Osteoporosis Bangor) in a

poster presentation at the American Society of Bone and Mineral Research

meeting. They reviewed data from a " hodgepodge " of several published

clinical trials carried out with PTH (mostly with teriparatide [which is PTH

1-34], but some used a PTH 1-84 product from NPS Pharmaceuticals).

A weekly injection of 60-mg PTH had very large effects on spine bone mineral

density (BMD), increasing it by 7.4%, which is greater than the increase

seen with bisphosphonates and as large or larger than the increases seen

with daily injections of PTH (about 4% with 20 mg/day and 7% with 40

mg/day).

However, the mechanism of action appears to be different weekly and daily

injections of PTH produce dramatically different effects on bone markers,

the researchers noted. With the weekly injection, bone formation increased

slightly and then decreased slightly (-15%), whereas with the daily

injections bone formation increased (150%+) " wildly, " Black commented. Also,

the effect on bone resumption was quite different: weekly dosing decreased

it slightly (-15%) while daily dosing increased it dramatically (100%+ to

300%+).

Black and Rosen posed the question, " Is less actually more? " Small doses of

PTH given weekly may be as or more effective than larger doses given daily,

they suggested, with several advantages: 1/7 of the dose, 1/7 of the cost,

and 1/7 of the risk of side effects, but 7 times greater compliance.

However, they emphasized that this is a hypothesis-generating exercise and

that the 2 dosing schedules need to be compared head-to-head in a clinical

trial. They are currently applying to the NIH for funding to perform such a

study, Black said.