How different is the once-weekly teriparatide from the daily one or the same?

Abstract

Teriparatide is a N-terminal fragment (1-34 amino acids) of parathyroid hormone (PTH) that can bind parathyroid hormone receptor type 1, PTH1R, to activate it similarly to the full-length (1-84 amino acids) hormone. Daily subcutaneous injection of teriparatide has been globally available as an anabolic therapy for severe osteoporosis since early 21st century. Once-weekly subcutaneous injection of teriparatide, 56.5 mg/injection instead of 20 mg for daily teriparatide injection, as an alternative therapeutic regimen was developed and approved in late 2013 in Japan. At this moment, once-weekly teriparatide is available in Japan and South Korea. Two independent papers focusing on once-weekly teriparatide in daily clinical practice are published in this issue of Osteoporosis and Sarcopenia [1,2]. Both of them have demonstrated that bone resorption markers did not increase with once-weekly teriparatide injections [1,2]. Changes of serum levels of N-terminal propeptide of type I procollagen (P1NP) as a bone formation marker were equivocal during the treatment, even though bone mineral density was consistently increased [1,2]. It might be unique in the onceweekly teriparatide, because teriparatide is known as a bone anabolic agent that stimulates bone metabolism, especially bone formation. Efficacy and safety of once-weekly teriparatide has been established in the Teriparatide Once-Weekly Efficacy Research (TOWER) study as a randomized double-blind placebo-controlled phase 3 trial for 72 weeks in patients with primary osteoporosis with high fracture risk [3]. Once-weekly injections of teriparatide reduced the risk of new vertebral fracture with a cumulative incidence of 3.1% in the teriparatide group, compared with 14.5% in the placebo group, and a relative risk of 0.20 (95% confidence interval, 0.09 to 0.45) [3]. At 72-week, teriparatide administration increased bone mineral density by 6.4%, 3.0%, and 2.3% at the lumbar spine, the total hip, and the femoral neck, respectively, compared with the placebo [3]. The risk reduction of new vertebral fracture with once-weekly teriparatide seemed not to be inferior to that with its daily injection [4], even though the amount of weekly administered teriparatide was 56.5 mg for once-weekly injection being much less than 140 mg a week for daily injection therapy. The once-weekly teriparatide is now clinically available as an alternative option for an anabolic therapy for osteoporosis. The question is how different is once-weekly teriparatide from its daily administration. First of all, once-weekly administration is more convenient to some patients than the once daily injection. More importantly, mechanisms for anabolic effects of once-weekly